Depressive disorders and symptoms are prevalent in patients with breast cancer, worsen over the course of cancer treatment, persist after cancer therapy, significantly impair quality of life, and decrease adherence to cancer therapy and survival. Yet, there are no established treatments for depression in breast cancer patients. As surviving cancer becomes increasingly common, there is an urgent need to develop an empirical basis to provide effective, evidence-based treatments to this population. We propose a randomized clinical trial to compare the efficacy of Interpersonal Psychotherapy (IPT), Problem-Solving Therapy (PST), and Brief Supportive Psychotherapy (BSP) in alleviating depressive symptoms and improving quality of life for breast cancer patients with DSM-IV major depressive disorder (MDD). IPT, a manualized, time-limited therapy, has shown repeated efficacy in treating MDD, and remarkable flexibility and efficacy across age ranges, cultures, formats, and modes of delivery. PST is a brief, manualized form of cognitive-behavioral therapy (CBT) that has been adapted to treat depression in cancer patients and shown highly promising results. BSP is a relatively unstructured psychotherapy commonly used in clinical practice that focuses on the patient's affect. It builds a strong therapeutic alliance through listening carefully and empathically to the patient, validating and encouraging toleration of the patient's emotions. It has shown promising results in depressed individuals with cancer and other medical illnesses. In addition to improvement in depressive symptoms, relationships between sociodemographic characteristics, clinical factors, depression treatment adherence, and outcomes care will be examined. Patients in each condition will receive 12 therapy sessions within a 16-week period, and will be followed for another 4 months to examine the stability of response. Our model is based on the existing literature, our long-standing experience in survivorship care of breast cancer patients, the theoretical appeal and promising data of the proposed treatments, and a broad range of preliminary data. In addition, the proposed study will yield insight into factors that influence key outcomes by examining mediators and moderators of treatment outcome. By investigating a theoretically-based treatment model with promising pilot data from a productive research team, we believe we can help generate the urgently needed empirical foundations for the provision of effective treatment to depressed breast cancer patients.